Santo Stefano Quisquina (Sicilian: Santu Stèfanu Quisquina) is a comune (municipality) in the Province of Agrigento in the Italian region Sicily, located about 60 kilometres (37 mi) south of Palermo and about 35 kilometres (22 mi) north of Agrigento.

It has strong ties with Tampa, in the United States, since its immigrants supplied over 60 percent of the Italian population of the city in the late 19th and early 20th century.

[3] Santo Stefano Quisquina stands at an altitude of 730 metres (2,400 ft) above sea level and borders the following municipalities: Alessandria della Rocca, Bivona, Cammarata, Casteltermini, Castronovo di Sicilia, San Biagio Platani.

The first nucleus of the present-day town probably dates back to the reign of Frederick II of Aragon (1296–1337), when it was a fief of Giovanni Caltagirone.

Its successive lords were Ruggero Sinisi, Guiscardo de Agijas, the Lacarns and the Ventimiglias.